This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The catalytic machinery for the bacterial phosphotriesterase (PTE) is capable of detoxifying organophosphates. Organophosphates such as tabun, sarin, soman, cyclosarin, and VX are among the most toxic and deadly nerve agents ever reported. Since these compounds are easy to synthesize and distribute they can be used as weapons. The active site of PTE will be re-engineered through rational and combinatorial mutagenesis to create a library of mutant enzyme with altered catalytic properties aimed at degrading organophosphates. Collaborators will test and optimize enzymes for their ability to act upon these nerve agents. Our objectives will be to determine high-resolution crystal structures to correlate structural details with the catalytic properties of the mutant enzymes.